Safety and immunogenicity of a trivalent recombinant PcpA, PhtD, and PlyD1 pneumococcal protein vaccine in adults, toddlers, and infants: A phase I randomized controlled study

Title: Safety and immunogenicity of a trivalent recombinant PcpA, PhtD, and PlyD1 pneumococcal protein vaccine in adults, toddlers, and infants: A phase I randomized controlled study

Authors: W. Abdullah Brooks and Lee-Jah Chang and Xiaohua Sheng and Robert Hopfer

Journal: Vaccine

Year: 2015

Abstract:

AbstractBackground Pneumococcal protein vaccines (PPrVs) may provide improved protection over currently available polysaccharide and conjugated polysaccharide vaccines. Here, we examined the safety and immunogenicity of a trivalent recombinant {PPrV} containing PcpA, PhtD, and PlyD1. Methods This was a phase I, single-center, randomized, observer-blind study with safety review between cohorts. Adults (18–۵۰ years; n = 30) and then toddlers (12–۱۳ months; n = 30) were randomized 2:1 to receive aluminum-adjuvanted trivalent {PPrV} (PPrV + adj) containing 50 μg per antigen or placebo. Infants (42–۴۹ days; n = 220) were next randomized to be injected at 6, 10, and 14 weeks of age with 10 μg {PPrV} + adj or placebo (n = 60; 2:1); 25 μg {PPrV} + adj, 25 μg unadjuvanted PPrV, or placebo (n = 100; 2:2:1); and 50 μg {PPrV} + adj or placebo (n = 60; 2:1). Solicited reactions were recorded for 7 days and unsolicited adverse events for 30 days after each vaccination. Concentrations of antibodies to the three vaccine antigens were measured by enzyme-linked immunosorbent assay. Results Tenderness/pain was the most frequent injection-site reaction. Abnormal crying and irritability (infants), loss of appetite (toddlers), and headache, malaise, and myalgia (adults) were the most frequent systemic reactions. Reactions were mostly mild or moderate, resolved within 3 days, were not adjuvant- or dose-dependent, and were not increased by repeated vaccination. No immediate adverse events, hypersensitivity reactions, or treatment-related serious adverse events were reported. In all {PPrV} + adj cohorts, at least 75% of subjects had a ≥۲-fold increase in all three antibody concentrations. In infants, antibody concentrations were higher with {PPrV} + adj than with unadjuvanted PPrV, higher with three than two vaccinations, and similar at the different vaccine doses. Conclusions The candidate trivalent {PPrV} was safe and immunogenic in adults, toddlers, and infants. Addition of aluminum adjuvant improved immunogenicity in infants without changing the safety profile.